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Treatment of Hypertension in the Elderly: A Major Challenge. Thomas G Pickering MD, D Phil Behavioral Cardiovascular Health and Hypertension Program Columbia Presbyterian Hospital. Treating older adults: Updates and Practical Approaches. Risks associated with high BP JNC 7 Guidelines

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treatment of hypertension in the elderly a major challenge

Treatment of Hypertension in the Elderly: A Major Challenge

Thomas G Pickering MD, D Phil

Behavioral Cardiovascular Health and Hypertension Program

Columbia Presbyterian Hospital

treating older adults updates and practical approaches

Treating older adults: Updates and Practical Approaches

Risks associated with high BP

JNC 7 Guidelines

Goals of treatment

Choice of drugs

Hypertension in the very old

Non-drug treatment

treating older adults updates and practical approaches1

Treating older adults: Updates and Practical Approaches

Risks associated with high BP

JNC 7 Guidelines

Goals of treatment

Choice of drugs

Hypertension in the very old

Non-drug treatment

continuous relation between blood pressure and risk of cvd
Continuous Relation Between Blood Pressure And Risk Of CVD

Stroke CHD

4

4

2

2

Relative Risk

1

1

0.5

0.5

0.25

0.25

76

84

91

98

105

76

84

91

98

105

Usual Diastolic Pressure (mm Hg)

MacMahon et al. Lancet. 1990;335:765.

stiffer arteries increase pulse wave velocity and pulse pressure
Stiffer Arteries Increase Pulse Wave Velocity And Pulse Pressure

Average Blood Pressure Waveform

Average Blood Pressure Waveform

Shoulder

Notch

Notch

Time (sec)

Time (sec)

52-year-Old

Normal Pressure Wave

81-year-Old

Early Pulse Wave Reflection

pulse pressure predicts risk best in older hypertensives a meta analysis
Pulse Pressure Predicts Risk Best In Older HypertensivesA Meta-Analysis

EWPHE (N=840)

Syst-Eur (N=4695)

Syst-China (N=2394)

Diastolic Pressure (mm Hg)

2-Year Risk Of End Point

Systolic Blood Pressure (mm Hg)

Blacher et al. Arch Intern Med. 2000;160.

slide8

60

60

50

50

40

40

30

30

20

20

Clinic

24-hr

10

10

Daytime

Nighttime

0

0

190

110

130

190

150

110

170

130

150

170

Ambulatory BP and Cardiovascular Disease

in the Elderly with Systolic Hypertension:

The Syst-Eur Study (N = 808)

Placebo

Active treatment

Cardiovascular disease

(per 1000 patient - year)

Staessen et al. JAMA 1999; 282: 539-46.

consequences of treating white coat hypertension syst eur study fagard et al circ 2000 102 1139
Consequences of Treating White Coat Hypertension (Syst-Eur study)(Fagard et al, Circ 2000; 102: 1139)

Placebo

Active

Change of Clinic SBP mmHg

White coat HTN

Mild HTN

Moderate HTN

consequences of treating white coat hypertension syst eur study fagard et al circ 2000 102 11391
Consequences of Treating White Coat Hypertension (Syst-Eur study)(Fagard et al, Circ 2000; 102: 1139)

Placebo

Active

Change of Daytime SBP mmHg

White coat HTN

Mild HTN

Moderate HTN

consequences of treating white coat hypertension syst eur study fagard et al circ 2000 102 11392
Consequences of Treating White Coat Hypertension (Syst-Eur study)(Fagard et al, Circ 2000; 102: 1139)

Rate of strokes per1000 pt-years

P<0.03

P=NS

P=NS

White coat HTN

Mild HTN

Moderate HTN

the white coat effect in the real world little et al bmj 2002 325 254

The White Coat Effect in the Real World(Little et al, BMJ 2002; 325: 254)

173 hypertensive patients in 3 general practices in the UK

Clinic (MD and RN), self-monitoring, and ABPM

White coat effect estimated as difference between other measures of BP and daytime BP:-

Physician 19/11 mmHg

Nurse 1 5/8 mmHg

Nurse 2 5/6 mmHg

Self-monitoring in clinic 10/13 mmHg

Self-monitoring at home 5/6 mmHg

jnc 7 self measurement of bp
JNC 7: Self-Measurement of BP
  • Provides information on:
    • Response to antihypertensive therapy
    • Improving adherence with therapy
    • Evaluating white-coat HTN
  • Home measurement of >135/85 mmHg is generally considered to be hypertensive.
  • Home measurement devices should be checked regularly.
slide15

Analysis of The Influence of the Morning Surge of BP on Stroke Incidence (Kario, Pickering et al)

analysis of the influence of the morning surge of bp on stroke incidence kario pickering et al

Analysis of The Influence of the Morning Surge of BP on Stroke Incidence (Kario, Pickering et al)

Cox regression analysis for clinical stroke events

Covariates RR P value

Age (10 yrs) 1.80 (1.21-2.69) 0.004

Male gender 1.42 (0.76-2.67) 0.266

BMI 0.98 (0.90-1.07) 0.663

24 hr SBP 1.37 (1.16-1.63 0.003

SCI 4.40 (1.95-10.1) 0.001

Morning BP surge* 1.29 (1.10-1.51) 0.001

Nocturnal BP fall* 0.88 (0.73-1.06) 0.167

Lowest sleep BP 1.05 (0.65-1.71) 0.837

* per 10 mmHg

treating older adults updates and practical approaches2

Treating older adults: Updates and Practical Approaches

Risks associated with high BP

JNC 7 Guidelines

Goals of treatment

Choice of drugs

Hypertension in the very old

Non-drug treatment

slide18

JNC 7: New Features and Key Messages

  • Forpersons over age 50, SBP is a more important than DBP as CVD risk factor.
  • Starting at 115/75 mmHg, CVD risk doubles with each increment of

20/10 mmHg throughout the BP range.

  • Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN.
  • Those with SBP 120–139 mmHg or DBP 80–89 mmHg should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD.
slide19

JNC 7: New Features and Key Messages

  • For persons over age 50, SBP is a more important than DBP as CVD risk factor.
  • Starting at 115/75 mmHg, CVD risk doubles with each increment of

20/10 mmHg throughout the BP range.

  • Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN.
  • Those with SBP 120–139 mmHg or DBP 80–89 mmHg should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD.
jnc 7 new features and key messages continued
JNC 7: New Features and Key Messages (Continued)
  • Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes.
  • Certain high-risk conditions are compelling indications for other drug classes.
  • Most patients will require two or more antihypertensive drugs to achieve goal BP.
  • If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.
jnc 7 new features and key messages continued1
JNC 7: New Features and Key Messages (Continued)
  • Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes.
  • Certain high-risk conditions are compelling indications for other drug classes.
  • Most patients will require two or more antihypertensive drugs to achieve goal BP.
  • If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.
treating older adults updates and practical approaches3

Treating older adults: Updates and Practical Approaches

Risks associated with high BP

JNC 7 Guidelines

Goals of treatment

Choice of drugs

Hypertension in the very old

Non-drug treatment

bp control rates
BP Control Rates

Trends inawareness, treatment, and control of high blood pressure in adults ages 18–74

Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6.

slide24

Characteristics of Patients with Uncontrolled Hypertension in the US: NHANES (Hyman et al, NEJM; 2001; 345: 479)

Predictors of Uncontrolled Hypertension

HTN Undiagnosed HTN Diagnosed

Factor Rel Risk Attrib Risk Rel Risk Attrib Risk

Age >65 7.69 0.46 2.08 0.32

Male sex 1.58 0.22 1.30 0.12

Black race 1.45 0.05 - -

MD visits 1.40 0.09 1.89 0.08

how far should bp be lowered in the elderly

How far should BP be lowered in the elderly?

Trial Starting BP Final BP

HOT 170 140-144

EWPHE 183 149

SHEP 170 144

Syst-Eur 174 151

Conclude: No evidence to support lowering BP to<140 mmHg

treating older adults updates and practical approaches4

Treating older adults: Updates and Practical Approaches

Risks associated with high BP

JNC 7 Guidelines

Goals of treatment

Choice of drugs

Hypertension in the very old

Non-drug treatment

trends in antihypertensive drug use kaplan 2003
Trends in Antihypertensive Drug Use(Kaplan 2003)

Diuretics

No. of prescriptions

(millions)

CCBs

Beta blockers

ARBs

ACEI

Alpha blockers

Year

limited efficacy of monotherapy in treating hypertension materson nejm 1993 328 914
Limited Efficacy of Monotherapy in Treating Hypertension (Materson NEJM 1993; 328: 914)

Patients Responding %

the antihypertensive and lipid lowering treatment to prevent heart attack trial allhat

ALLHAT

U.S. Department of

Health and Human Services

National Institutes

of Health

National Heart, Lung, and Blood Institute

Major Outcomes in High Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

The ALLHAT Collaborative Research Group

Sponsored by the National Heart, Lung, and Blood Institute (NHLBI)

JAMA. 2002;288:2981-2997

slide30

ALLHAT

Compared to chlorthalidone:

SBP significantly higher in the amlodipine group (~1 mm Hg) and the lisinopril group (~2 mm Hg).

Compared to chlorthalidone:

DBP significantly lower in the amlodipine group (~1 mm Hg).

BP Results by Treatment Group

slide31

ALLHAT

.2

.16

.12

Cumulative CHD Event Rate

.08

.04

0

0

1

2

3

4

5

6

7

Years to CHD Event

Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group

Chlorthalidone

Amlodipine

Lisinopril

slide32

ALLHAT

.1

.08

.06

Cumulative Stroke Rate

.04

.02

0

0

1

2

3

4

5

6

7

Years to Stroke

Cumulative Event Rates for Stroke by ALLHAT Treatment Group

Chlorthalidone

Amlodipine

Lisinopril

overall conclusions

ALLHAT

Overall Conclusions

Because of the superiority of thiazide-type diuretics in preventing one or more major forms of CVD and their lower cost, they should be the drugs of choice for first-step antihypertensive drug therapy.

anbp2 australian trial of acei vs diuretics in the elderly wing et al nejm 2003 348 583
ANBP2: Australian Trial of ACEI vs Diuretics in the Elderly (Wing et al NEJM, 2003; 348: 583)
  • Subjects were 6083 hypertensives aged 65-84 , BP >160/90 mmHg
  • Randomized to ACEI (Enalapril) or Diuretic (HCTZ)
  • Significant 11% (just) reduction in combined CV events for ACEI group (17% in men, 0 in women)
  • Blood Pressures were identical for the two groups throughout the study
comparison of allhat and anbp2

Comparison of ALLHAT and ANBP2

Study Conclusions

ALLHAT- Diuretics Better than ACEI

ANBP2- ACEI better than Diuretics

Can they be reconciled?

Other studies show that ACEI prevent heart failure

Higher incidence of heart failure in ALLHAT ACEI group occurred early, and may have been due to diuretic withdrawal

Higher incidence of stroke in ALLHAT ACEI group may have been due to higher BP

Higher percentage of blacks in ALLHAT- blacks did better with stroke, coronary endpoints, and heart failure In D than in ACEI group

slide36
PROGRESS & PATS: Effects of Diuretics and ACEI on Recurrent Stroke(Messerli et al, Arch Int Med 163: 2557, 2003)

PROGRESS PATS PROGRESS Perindopril Indapamide Both

Reduction of SBP or stroke

slide37
LIFE: Reduction of stroke but not MI with Losartan inIsolated Systolic Hypertension(Kjeldsen et al JAMA 2002: 288: 1491)
effects of diuretics and beta blockers on cardiovascular mortality jnc vi
Effects of Diuretics and Beta Blockers on Cardiovascular Mortality (JNC VI)

Drug Dose No. RR (95% CI)

Diuretics High 11 0.78 (0.62-0.97)

Diuretics Low 4 0.76 (0.65-0.89)

Beta blockers 4 0.89 (0.76-1.05)

0.4 0.7 1.0 RR (95% CI)

Treatment Treatment Better Worse

slide39
Prevention of Dementia with Calcium Channel Blocker Treatment in ISH- Syst-Eur (Forette et al, Arch Int Med 2002: 162: 2046)
treating older adults updates and practical approaches5

Treating older adults: Updates and Practical Approaches

Risks associated with high BP

JNC 7 Guidelines

Goals of treatment

Choice of drugs

Hypertension in the very old

Non-drug treatment

hypertension in the very old bulpitt j hum hyp 1994 8 603

Hypertension in the Very Old(Bulpitt J Hum Hyp 1994; 8:603)

Four Reasons why Hypertension may be Different in the Elderly

They are survivors

Many have taken years to become ‘hypertensive’

Some have atheromatous renal artery stenosis

Diastolic pressure falls in the elderly

bp and survival in the very old mattila et al bmj 1988 296 887
BP and Survival in the Very Old(Mattila et al, BMJ 1988:296; 887)

561 Finns aged 84-102 (mean 88)

Systolic Pressure

mmHg

5 year survival

Diastolic Pressure

mmHg

hypertension in the very elderly trial hyvet

Hypertension in the Very Elderly Trial (HYVET)

2100 hypertensives aged >80 randomised to No treatment, ACEI, or diuretic

5 year F/U

Endpoint is a 40% reduction in stroke

hyvet results of pilot study bulpitt et al j hypertens 2003 21 2409

HYVET: Results of Pilot Study(Bulpitt et al, J Hypertens 2003: 21: 2409)

1283 hypertensive patients aged >80 randomized to Diuretic, ACEI, or no treatment

Target BP <150/80; follow-up 13 months

Results:

Total mortality: no effect

CV mortality: no effect

Stroke events: Diuretics RR 0.313, p<0.01

ACEI RR 0.629, p= 0.21

treating older adults updates and practical approaches6

Treating older adults: Updates and Practical Approaches

Risks associated with high BP

JNC 7 Guidelines

Goals of treatment

Choice of drugs

Hypertension in the very old

Non-drug treatment

conclusions hypertension in the elderly

Conclusions: Hypertension in the Elderly

An increasing problem with the ageing of the US population

Related to increased stiffness of arteries

Importance of white coat HTN, and out-of-office monitoring

Diuretics drugs of choice, with addition of others- emphasis on combination Rx

BP control is more important than drugs used

Include lifestyle modifications

Benefits of treatment in very old (>85) are unproven, but diuretics may be protective